79965-10-9

Basic information

• Product Name: N-4-METHOXYPHENYLRETINAMIDE
• Synonyms: N-4-METHOXYPHENYLRETINAMIDE;N-(4-Methoxyphenyl)-all-trans-retinaMide;N-(p-Methoxyphenyl)retinaMide
• CAS NO: 79965-10-9
• Molecular Formula: C27H35NO2
• Molecular Weight: 405.57
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Retinoids
• Mol File: 79965-10-9.mol

Chemical Properties

• Melting Point: 157-161°C
• Boiling Point: 585.3°C at 760 mmHg
• Flash Point: 307.8°C
• Appearance: /
• Density: 1.046g/cm³
• Vapor Pressure: 1.1E-13mmHg at 25°C
• Refractive Index: 1.584
• Storage Temp.: Amber Vial, -20°C Freezer, Under Inert Atmosphere
• Stability: Light Sensitive - Protect from Light Exposure
• CAS DataBase Reference: N-4-METHOXYPHENYLRETINAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: N-4-METHOXYPHENYLRETINAMIDE(79965-10-9)
• EPA Substance Registry System: N-4-METHOXYPHENYLRETINAMIDE(79965-10-9)

Safety Data

• Hazardous Substances Data: 79965-10-9(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
N-4-METHOXYPHENYLRETINAMIDE is used as a chemopreventive agent for the chemoprevention and growth modulation of oncogene-induced prostate cancer. It is particularly effective in the mouse prostate reconstitution model system and may be effective for the chemoprevention of human prostate cancer. Its application in this field is due to its ability to modulate the growth of oncogene-induced prostate cancer cells, offering a potential therapeutic strategy for the prevention and treatment of prostate cancer.

InChI:InChI=1/C27H35NO2/c1-20(12-17-25-22(3)11-8-18-27(25,4)5)9-7-10-21(2)19-26(29)28-23-13-15-24(30-6)16-14-23/h7,9-10,12-17,19H,8,11,18H2,1-6H3,(H,28,29)/b10-7+,17-12+,20-9-,21-19-

Upstream product

• 53839-60-4 retinoyl chloride 
• 104-94-9 4-methoxy-aniline 
• 302-79-4 all-trans-retinoic-acid 
• 67-56-1 methanol 
• 106864-00-0 uridine 5'-diphosphoglucuronic acid 
• 65646-68-6 N-(4-hydroxyphenyl)-all-trans-retinamide 

Relevant articles and documents

Fenretinide derivatives act as disrupters of interactions of serum retinol binding protein (sRBP) with transthyretin and the sRBP receptor

Serum retinol binding protein (sRBP) is released from the liver as a complex with transthyretin (TTR), a process under the control of dietary retinol. Elevated levels of sRBP may be involved in inhibiting cellular responses to insulin and in generating first insulin resistance and then type 2 diabetes, offering a new target for therapeutic attack for these conditions. A series of retinoid analogues were synthesized and examined for their binding to sRBP and their ability to disrupt the sRBP-TTR and sRBP-sRBP receptor interactions. A number inhibit the sRBP-TTR and sRBP-sRBP receptor interactions as well as or better than Fenretinide (FEN), presenting a potential novel dual mechanism of action and perhaps offering a new therapeutic intervention against type 2 diabetes and its development. Shortening the chain length of the FEN derivative substantially abolished binding to sRBP, indicating that the strength of the interaction lies in the polyene chain region. Differences in potency against the sRBP-TTR and sRBP-sRBP receptor interactions suggest variant effects of the compounds on the two loops of sRBP guarding the entrance of the binding pocket that are responsible for these two protein-protein interactions.

Characterization of the metabolism of fenretinide by human liver microsomes, cytochrome P450 enzymes and UDP-glucuronosyltransferases

Background and Purpose Fenretinide (4-HPR) is a retinoic acid analogue, currently used in clinical trials in oncology. Metabolism of 4-HPR is of particular interest due to production of the active metabolite 4-oxo 4-HPR and the clinical challenge of obtaining consistent 4-HPR plasma concentrations in patients. Here, we assessed the enzymes involved in various 4-HPR metabolic pathways. Experimental Approach Enzymes involved in 4-HPR metabolism were characterized using human liver microsomes (HLM), supersomes over-expressing individual human cytochrome P450s (CYPs), uridine 5-diphospho-glucoronosyl transferases (UGTs) and CYP2C8 variants expressed in Escherichia coli. Samples were analysed by high-performance liquid chromatography and liquid chromatography/mass spectrometry assays and kinetic parameters for metabolite formation determined. Incubations were also carried out with inhibitors of CYPs and methylation enzymes. Key Results HLM were found to predominantly produce 4-oxo 4-HPR, with an additional polar metabolite, 4-hydroxy 4-HPR (4-OH 4-HPR), produced by individual CYPs. CYPs 2C8, 3A4 and 3A5 were found to metabolize 4-HPR, with metabolite formation prevented by inhibitors of CYP3A4 and CYP2C8. Differences in metabolism to 4-OH 4-HPR were observed with 2C8 variants, CYP2C8 4 exhibited a significantly lower Vmax value compared with 1. Conversely, a significantly higher Vmax value for CYP2C8 4 versus 1 was observed in terms of 4-oxo formation. In terms of 4-HPR glucuronidation, UGTs 1A1, 1A3 and 1A6 produced the 4-HPR glucuronide metabolite. Conclusions and Implications The enzymes involved in 4-HPR metabolism have been characterized. The CYP2C8 isoform was found to have a significant effect on oxidative metabolism and may be of clinical relevance.

Solid phase-assisted synthesis and screening of a small library of N-(4-hydroxyphenyl)retinamide (4-HPR) analogs

Using solid phase-assisted synthesis and purification, a 49 member library of analogs of the mammary tumor chemopreventive retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been prepared. After prescreening for growth inhibitory activity in human mammary tumor cells (MCF-7) in culture, most of those analogs which showed activity (12 of them) were assayed for apoptosis-inducing activity in the MCF-7 cells. At least 3 of the analogs (13, 24, and 28) showed activity approaching that of 4-HPR.